St. John's Wort (Hypericum perforatum L.) is a bushy perennial with yellow flowers which blooms around St. John the Baptist's day in June. Commercial products are derived from the dried flowering tops or aerial parts of Hypericum perforatum L.; these parts are harvested shortly before or during the flowering period. Hypericum preparations include the dried herb (chopped or powdered), alcoholic extract, oil, and tincture.
Hypericum contains some very common plant constituents including flavonoid derivatives such as rutin, quercitrin and hypericin, biflavonoids such as amentoflavone, and essential oils. Active ingredients of Hypericum, which are specific to St. John's Wort, include the naphthodianthrones, such as cyclopseudohypericin, hypericin, hyperforin, isohypericin, photohypericin and psuedohypericin.
Hypericum extract has been used for the treatment of mild to moderate mental depression. All antidepressant medications made from St. John's Wort are based on methanol or ethanol extracts of the herb, with a solvent-to-herb ratio of 4:1 to 7:1. The highest yields of active antidepressant principles appear to be obtained by extracting the dried herb with aqueous methanol containing 20 to 40% water in darkness with temperatures raised only briefly to 60 to 80.degree. C.
Hypericum oil is used in folk medicine as a traditional topical remedy for wounds and burns. Hypericum oil is typically made by macerating the ground fresh flowers in olive oil in a sealed vessel.
In folk medicine and traditional systems of medicine, various species of Hypericum have been used orally to treat anxiety, bedwetting, dyspepsia, excitability, exhaustion, fibrositis, gastritis, gout, hemorrhage, pulmonary complaints, rheumatism, sciatica, and swelling. It also has been used orally as anthelmintic, an antidiarrheal, and a diuretic. Various dosage forms of Hypericum have been used topically as an astringent and to treat injuries or conditions such as blisters, burns, cuts, hemorrhoids, inflammation, insect bites, itchiness, redness, sunburns, and wounds.
Hypericum with or without light therapy may be useful for the treatment of seasonal affective disorder but studies to date have used too few subjects to determine its efficacy. Light therapy combine with Hypericum may increase the risk of phototoxicity in light skinned patients. Hypericum is being combined with other products such as ma huang (ephedra) and promoted for weight loss as an alternative to prescription weight loss medications that have been taken off the market.
Some in vitro and in vivo studies have found that hypericum constituents may possess antiviral properties. In vitro studies suggest that hypericum constituents have antiviral activity against cytomegalovirus, herpes simplex, human immunodeficiency virus type 1, influenza virus A, Moloney murine leukemia virus, and sindbis virus. One in vivo study, in mice, found that low doses of hypericin and psuedohypericin prevented retroviral-induced diseases.
Of all the medical uses of St. John's Wort, the use of hypericum extracts for the treatment of mild to moderate depression is the most extensive. Standardized extracts of St. John's Wort are sold in pharmacies throughout Europe, and are in fact among the most popular OTC "phytomedicines" sold in EEC countries. Among the most widely prescribed antidepressants in the United States are Prozac.RTM. from Eli Lilly, Zoloft.RTM. from Pfizer and Praxil.RTM. from SmithKline Beecham. The worldwide sales of the top selling antidepressants are approximately $4.8 billion. As people experience adverse side-effects from prescription antidepressants, there has been a concomitant rise in the use of St. John's Wort and other herbs as natural antidepressants. Several herbal formulations, purporting to be natural substitutes for Prozac.RTM., are already being marketed.
The alcohol extract of St. John's Wort enjoys a reputation as an effective antidepressant. The mechanisms of action by which the hypericum extract acts as an antidepressant are not fully understood. Some in vivo studies using, mouse or rat brain synatosomes have indicated that hypericum extract inhibits the synaptosomal uptake of serotonin, dopamine, and norepinephrine. Most in vivo studies have indicated that hypericum compounds competitively inhibit subtype A monoamine oxidase (MAO). Subtype A MAO inhibition, involving dopamine, norepinephrine, and serotonin, is thought to be effective in the treatment of depression. The National Institutes of Health has initiated a long term, multicenter, double-blinded clinical trial to study the effects of a hypericum extract (IL-160 manufactured by Kira), a placebo, and a selective serotonin re-uptake inhibitor (Zoloft which is manufactured by Pfizer) for the treatment of major depression.
IL-160, the most studied extract of Hypericum, is manufactured with 80% methanol in a solvent-to-herb ratio of 7-4:1 and standardized on 0.3 wt. percent content of hypericin. Recent findings indicate that Hypericum perforatum may have up to 10 active constituents with limited evidence that at least one of them, hyperforin, could be more active than hypericin. At least two manufacturers (of Perika and Movana tablets) are now standardizing their products against 3.0 wt. percent hyperforin. There are indications that hyperforin is very unstable and must be stabilized by the addition of excipients including antioxidants.
A method for producing fractions of Hypericum comprising different active ingredients or proportions of active ingredients is desired. Products incorporating such fractions could be marketed for different indications.